Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

Effects of Pyruvate Kinase M2 (PKM2) Gene Deletion on Astrocyte-Specific Glycolysis and Global Cerebral Ischemia-Induced Neuronal Death.

Ischemic stroke is caused by insufficient blood flow to the brain. Astrocytes have a role in bidirectionally converting pyruvate, generated via glycolysis, into lactate and then supplying it to neurons through astrocyte-neuron lactate shuttle (ANLS). Pyruvate kinase M2 (PKM2) is an enzyme that dephosphorylates phosphoenolpyruvate to pyruvate during glycolysis in astrocytes. We hypothesized that a reduction in lactate supply in astrocyte PKM2 gene deletion exacerbates neuronal death. Mice harboring a PKM2 gene deletion were established by administering tamoxifen to Aldh1l1-CreERT2; PKM2f/f mice. Upon development of global cerebral ischemia, mice were immediately injected with sodium l-lactate (250 mg/kg, i.p.). To verify our hypothesis, we compared oxidative damage, microtubule disruption, ANLS disruption, and neuronal death between the gene deletion and control subjects. We observed that PKM2 gene deletion increases the degree of neuronal damage and impairment of lactate metabolism in the hippocampal region after GCI. The lactate administration groups showed significantly reduced neuronal death and increases in neuron survival and cognitive function. We found that lactate supply via the ANLS in astrocytes plays a crucial role in maintaining energy metabolism in neurons. Lactate administration may have potential as a therapeutic tool to prevent neuronal damage following ischemic stroke.

2,4-Diacetylphloroglucinol Reduces Beta-Amyloid Production and Secretion by Regulating ADAM10 and Intracellular Trafficking in Cellular and Animal Models of Alzheimer's Disease.

There is currently no effective treatment against Alzheimer's disease (AD), although many strategies have been applied to reduce beta-amyloid (Aß) levels. Here, we investigated 2,4-diacetylphloroglucinol (DAPG) effects on Aß levels and mechanisms of action. DAPG was the most effective phloroglucinol derivative for reducing Aß levels, without being toxic, in various models including HEK293 cells overexpressing Swedish mutant amyloid precursor protein (APP) (293sw), primary astrocytes isolated from APPsw/PS1dE9 transgenic mice, and after intrahippocampal injection of DAPG in APPsw/PS1dE9 transgenic mice. DAPG-mediated Aß reduction was associated with increased soluble APPα (sAPPα) levels mediated by a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) but not ADAM17. ADAM10 inhibition in DAPG-treated cells prevented the effects on sAPPα but only partly on intracellular and secreted Aß. To identify regulators of sAPPα and Aß secretion, various inhibitors of intracellular trafficking were administered with DAPG. Brefeldin A (BFA) reversed DAPG-mediated changes in Aß secretion in 293sw cells, whereas golgicide A (GCA) and BFA were effective in primary astrocytes, indicating a cell type-specific regulation of the trafficking. Moreover, GCA or BFA effects on sAPPα, but not Aß, levels in primary astrocytes resembled those of ADAM10 inhibition, indicating at least partly independent trafficking pathways for sAPPα and Aß. In conclusion, DAPG might be a promising drug candidate against AD regulating ADAM10 and intracellular trafficking, but optimizing DAPG ability to cross the BBB will be needed.

Unexpected beta-amyloid production by middle doses of resveratrol through stabilization of APP protein and AMPK-mediated inhibition of trypsin-like proteasome activity in a cell model of Alzheimer's disease.

Resveratrol is a drug candidate used for Alzheimer's disease (AD) and shows beneficial effects in various toxicity and production models, although recent clinical trial data did not show satisfactory results. Here we demonstrated the potential side effects of resveratrol in AD. We demonstrated resveratrol concentration- and time-dependent Aß production using Aß secreted cellular model and analyzed resveratrol-related molecular signaling. In Swedish mutant of APP (APPsw) stably expressing cells, treatment with a middle dose of resveratrol for 24 h unexpectedly increased Aß production, but higher concentrations or shorter treatment durations did not. Resveratrol-mediated Aß production was caused by an increase in APP protein levels associated with proteasome-dependent regulation of APP stability. Inhibition of AMPK, cAMP production, and epac1 attenuated Aß production and APP increase by resveratrol, which blocked the inhibition of trypsin-like proteasomal activity. In addition, high-dose resveratrol decreased Aß secretion and ß-secretase activity at any treatment duration. Our data suggest that an appropriate dose of resveratrol can paradoxically increase Aß production via stabilization of APP protein in an AMPK-proteasome signaling-dependent manner, which provides mechanistic insights into prior unsatisfactory clinical outcomes and the future clinical use of resveratrol.

Factors affecting the survival of early COVID-19 patients in South Korea: An observational study based on the Korean National Health Insurance big data.

OBJECTIVES: This study aimed to identify the survival rate and explore factors affecting survival among early COVID-19 patients in South Korea. METHODS: Data reported by the Korea Disease Control and Prevention Agency (KDCA), up to 15 July, when COVID-19 was confirmed were used as research data in connection with the National Health Insurance Service's (NHIS) national health information database. The final analysis targets were 12,646 confirmed patients and 303 deaths. The survival rate of patients with COVID-19 was estimated through Kaplan-Meier survival analysis. Cox proportional hazard regression analysis was performed to search for factors affecting survival. RESULTS: When looking at the survival rate by age group for men and women, the 28-day survival rate for men aged >80 years was 77% and 73% at 42 days, while 83% and 81% for women. Men had a worse survival rate than women. For chronic diseases, the highest risk of mortality was observed in malignant neoplasms of the respiratory and urogenital systems, followed by diseases of the urinary system and diabetes. CONCLUSIONS: The number of COVID-19 deaths was highest the next day after initial diagnosis. The case fatality rate was high in males, older age, and chronic diseases.

CD99-PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor.

The epidermal growth factor receptor (EGFR), a member of ErbB receptor tyrosine kinase (RTK) family, is activated through growth factor-induced reorganization of the actin cytoskeleton and subsequent dimerization. We herein explored the molecular mechanism underlying the suppression of ligand-induced EGFR dimerization by CD99 agonists and its relevance to tumor growth in vivo. Epidermal growth factor (EGF) activated the formation of c-Src/focal adhesion kinase (FAK)-mediated intracellular complex and subsequently induced RhoA-and Rac1-mediated actin remodeling, resulting in EGFR dimerization and endocytosis. In contrast, CD99 agonist facilitated FAK dephosphorylation through the HRAS/ERK/PTPN12 signaling pathway, leading to inhibition of actin cytoskeletal reorganization via inactivation of the RhoA and Rac1 signaling pathways. Moreover, CD99 agonist significantly suppressed tumor growth in a BALB/c mouse model injected with MDA-MB-231 human breast cancer cells. Taken together, these results indicate that CD99-derived agonist ligand inhibits epidermal growth factor (EGF)-induced EGFR dimerization through impairment of cytoskeletal reorganization by PTPN12-dependent c-Src/FAK inactivation, thereby suppressing breast cancer growth.

Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma.

Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of the poor drug distribution in the brain. In this study, we investigated the therapeutic efficacy of cancer-targeting arginyl-glycyl-aspartic tripeptide (RGD) conjugated paclitaxel (PTX)-loaded nanoparticles (NPs) against GBM by nose-to-brain delivery. Our results demonstrated that RGD-modified PTX-loaded NPs showed cancer-specific delivery and enhanced anticancer effects in vivo. The intranasal (IN) inoculation of RGD-PTX-loaded NPs effectively controls the tumor burden (75 ± 12% reduction) by inducing apoptosis and/or inhibiting cancer cell proliferation without affecting the G0 stage of normal brain cells. Our data provide therapeutic evidence supporting the use of intranasally delivered cancer-targeted PTX-loaded NPs for GBM therapy.

The coverage rates for influenza vaccination and related factors in Korean adults aged 50 and older with chronic disease: based on 2016 Community Health Survey data.

OBJECTIVES: This study aims to identify the coverage rates for influenza vaccination and related factors depending on chronic disease in Korean adults aged 50 and older. METHODS: The 2016 Korea Community Health Survey was used for analysis. Chi-square test was performed to investigate the coverage rates for influenza vaccination depending on chronic disease, and a multiple logistic regression analysis was used to identify the factors associated with influenza vaccination, by chronic disease. RESULTS: In men with ≥1 chronic disease, 39.8% of 50-64 years of age, and 86.8% of elderly (over 65 years of age) received influenza vaccination. In women with ≥1 chronic disease, 58.7% of 50-64 years of age, and 89.9% of elderly (over 65 years of age) received influenza vaccination (p<0.001). The chronic diseases associated with influenza vaccination were hypertension (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.19 to 1.37), diabetes (OR, 1.41; 95% CI, 1.28 to 1.55) in men aged 50-64, hypertension (OR, 1.34; 95% CI, 1.20 to 1.49), diabetes (OR, 1.17; 95% CI, 1.02 to 1.33), chronic cardiovascular disease (OR, 1.31; 95% CI, 1.07 to 1.60) in elderly (over 65 years of age). In women aged 50-64, hypertension (OR, 1.39; 95% CI, 1.30 to 1.49), diabetes (OR, 1.51; 95% CI, 1.35 to 1.68), chronic cardiovascular disease (OR, 1.31; 95% CI, 1.05 to 1.64), and hypertension (OR, 1.55; 95% CI, 1.40 to 1.71), diabetes (OR, 1.27; 95% CI, 1.12 to 1.43) in elderly (over 65 years of age). CONCLUSIONS: Populations in aged 50-64 are recommendation subject for vaccination or classified as high-risk group in case with chronic disease. Though subject over 60 years old is age close to the elderly, the coverage rates for vaccination was low. It is necessary to devise strategies to raise the coverage rates for vaccination.

Factors related to cancer screening behaviors.

OBJECTIVES: This study aimed to investigate the factors related to cancer screening behaviors (CSB). METHODS: The 2014 Korean Community Health Survey used for analysis. The dependent variable was CSB, and the independent variables were demographic, health behavioral, and regional factor. Propensity score matching (PSM) used to control health behavior and regional factors, which were influencing CSB. For statistical analysis, chi-square test and logistic regression analysis used. RESULTS: Logistic regression analysis after PSM showed that gender, age, marital status, educational level, monthly household income, employment type, alcohol drinking, smoking, body mass index group, chronic disease, and subjective health status influenced the CSB, there were statistical differences. CONCLUSIONS: To improve cancer screening (CS), it is necessary to educate individuals on the need for CS and to carry out a personalized CS program based on an individual's demographic status and health behavior.

Trichostatin A and Sirtinol Regulate the Expression and Nucleocytoplasmic Shuttling of Histone Deacetylases in All-Trans Retinoic Acid-Induced Differentiation of Neuroblastoma Cells.

Neuroblastoma cell differentiation is a valuable model for studying therapeutic methods in neuroblastoma and the mechanisms of neuronal differentiation. Here, we used trichostatin A (TSA) and sirtinol, which are inhibitors of cHDACs and sirtuins, respectively, to show that classical histone deacetylases (cHDACs) and sirtuins (silent mating type information regulation 2 homolog; SIRTs) affect all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells. After first determining neurite elongation and expression levels of tyrosine hydroxylase and high size neurofilament as useful differentiation markers, we observed that TSA increased neuroblastoma cell differentiation, while sirtinol had the antagonistic effect of decreasing it. The changes were also associated with the nucleocytoplasmic shuttling of cHDACs and sirtuins. ATRA significantly decreased the nuclear to cytoplasmic ratio of SIRT1 and SIRT2.1, while sirtinol inhibited that of SIRT1, and TSA increased that of SIRT1 and SIRT2.1 during early differentiation. Moreover, the effect of the sirtinol-related signal was located upstream for cHDACs and sirtuins total expression, and downstream for their subcellular localization compared with that for the TSA-related signal. These results provide a mechanistic understanding of differentiation in neuroblastoma cells and indicate that cHDACs and sirtuins are critical therapeutic targets for neuroblastoma.

The Association Between Shift Work and Health Behavior: Findings from the Korean National Health and Nutrition Examination Survey.

BACKGROUND: Shift workers are increasing worldwide, and various negative health effects of shift work have been reported. This study aimed to evaluate the relationship between shift work and health behavior. METHODS: This cross-sectional study included a total of 11,680 Korean adults (6,061 men and 5,619 women) aged ≥20 years old who participated in the Fifth Korean National Health and Nutrition Examination Survey, 2010-2012. Multiple logistic regression analysis was performed to evaluate the association between shift work and health behavior after adjusting for covariates. RESULTS: In men, shift work was associated with an increased risk of inadequate sleep (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.00 to 1.40) compared to day work. In women, shift work was associated with an increased risk of smoking (OR, 1.73; 95% CI, 1.34 to 2.22) and inadequate sleep (OR, 1.24; 95% CI, 1.05 to 1.47) compared to day work. In an age-stratified subgroup analysis, female shift workers aged ≥50 years old demonstrated an increased risk of smoking (OR, 5.55; 95% CI, 3.60 to 8.55), alcohol consumption (OR, 2.22; 95% CI, 1.53 to 3.23), and inadequate sleep (OR, 1.50; 95% CI, 1.10 to 2.05) compared to female day workers. CONCLUSION: Shift work is associated with worse health behavior, and this is most evident in women aged ≥50 years. Targeted strategies to reduce the negative health effects of shift work should be implemented, with consideration of shift workers' demographic characteristics.

Inhibition of Mitochondrial Clearance and Cu/Zn-SOD Activity Enhance 6-Hydroxydopamine-Induced Neuronal Apoptosis.

Parkinson's disease (PD) is a common movement disorder among neurodegenerative diseases, involving neuronal cell death in the substantia nigra of the midbrain. Although mechanisms of cell death in PD have been studied, the exact molecular pathogenesis is still unclear. Here, we explore the relationship between two types of cell death, autophagy and apoptosis, which have been studied separately in parkinsonian mimetic model of 6-hydroxydopamine (6-OHDA). 6-OHDA induced autophagy firstly and then later inhibition of autophagy flux occurred with apoptosis. The apoptosis was prevented by treatment of pan-caspase inhibitor, zVAD-fmk (benzyloxycarbonyl-VAD-fluoromethylketone (zVAD)), or early phase inhibitor of autophagy, 3-methyladenine (3-MA), indicating that autophagic induction was followed by the apoptosis. Interestingly, late step inhibitor of autophagy, bafilomycin A1 (BafA), aggravated 6-OHDA-induced apoptosis. This was associated with mitochondrial abnormality such as the inhibition of damaged mitochondrial clearance and aberrant increase of extracellular oxygen consumption. Furthermore, treatment of BafA did not inhibit 6-OHDA-mediated superoxide formation but strongly reduced the hydrogen peroxide production to below basal levels, indicating failure from superoxide to hydrogen peroxide. These results were accompanied by a lowered expression and activity of copper/zinc superoxide dismutase (Cu/Zn-SOD) but not of manganese SOD (MnSOD) and catalase. Thus, the present study suggests that crosstalk among apoptosis, autophagy, and oxidative stress is a causative factor of 6-OHDA-induced neuronal death and provides a mechanistic understanding of PD pathogenesis.

Facial skin fistula as a postoperative complication related to maxillary sinus grafting: A case report.

Maxillary sinus elevation has become an important surgical procedure in dental implant surgery. This procedure may induce a variety of postoperative complications including infection, perforation of the sinus membrane, and maxillary sinusitis. However, postoperative infections are relatively infrequent. In this report, an unusual form of infection resulting in a facial skin fistula following maxillary sinus elevation is described.

Beta-amyloid oligomers induce early loss of presynaptic proteins in primary neurons by caspase-dependent and proteasome-dependent mechanisms.

Beta-amyloid is a major pathogenic molecule for Alzheimer's disease (AD) and can be aggregated into a soluble oligomer, which is a toxic intermediate, before amyloid fibril formation. Beta-amyloid oligomers are associated closely with early synaptic loss in AD. However, it is still unknown which synaptic proteins are involved in the synaptotoxicity, and a direct comparison among the synaptic proteins should also be addressed. Here, we investigated changes in the expression of several presynaptic and postsynaptic proteins in primary neurons after treatment with a low-molecular weight and a high-molecular weight beta-amyloid oligomer. Both oligomers induced early neuronal dysfunction after 4 h and significantly reduced presynaptic protein (synaptophysin, syntaxin, synapsin, and synaptotagmin) expression. However, the expression of postsynaptic proteins (PSD95, NMDAR2A/B, and GluR2/3), except NMDAR1 was not reduced, and some protein expression levels were increased. Glutamate treatment, which is correlated with postsynaptic activation, showed more postsynaptic-specific protein loss compared with beta-amyloid oligomer treatment. Finally, the caspase inhibitor zVAD and the proteasomal inhibitor MG132 attenuated presynaptic protein loss. Thus, our data showed changes in synaptic proteins by beta-amyloid oligomers, which provides an understanding of early synaptotoxicity and suggests new approaches for AD treatment.

Calcifying cystic odontogenic tumor associated with ameloblastic fibro-odontoma of the anterior mandible.

Calcifying cystic odontogenic tumor, which was formerly named calcifying odontogenic cyst, is a benign odontogenic tumor containing clusters of ghost cells within ameloblastic epithelium. Calcifying cystic odontogenic tumors have been associated with other odontogenic tumors, a finding that is a rare event in other types of odontogenic cysts or tumors. This report describes a case of hybrid odontogenic tumor composed of calcifying cystic odontogenic tumor and ameloblastic fibroma-odontoma of the anterior mandible that occurred in a 4-year-old Korean girl.

Oxyhalogen-sulfur chemistry: kinetics and mechanism of oxidation of N-acetyl homocysteine thiolactone by acidified bromate and aqueous bromine.

N-acetyl homocysteine thiolactone (NAHT), medically known as citiolone, can be used as a mucolytic agent and for the treatment of certain hepatic disorders. We have studied the kinetics and mechanisms of its oxidation by acidic bromate and aqueous bromine. In acidic bromate conditions the reaction is characterized by a very short induction period followed by a sudden and rapid formation of bromine and N-acetyl homocysteine sulfonic acid. The stoichiometry of the bromate-NAHT reaction was deduced to be: BrO3(-) + H2O + CH3CONHCHCH2CH2SCO → CH3CONHCHCH2CH2(SO3H)COOH + Br(-) (S1) while in excess bromate it was deduced to be: 6BrO3(-) + 5CH3CONHCHCH2CH2SCO + 6H(+) → 3Br2 + 5CH3CONHCHCH2CH2(SO3H)COOH + 2H2O (S2). For the reaction of NAHT with bromine, a 3:1 stoichiometric ratio of bromine to NAHT was obtained: 3Br2 + CH3CONHCHCH2CH2SCO + 4H2O → 6Br(-) + CH3CONHCHCH2CH2(SO3H)COOH + 6H(+) (S3). Oxidation occurred only on the sulfur center where it was oxidized to the sulfonic acid. No sulfate formation was observed. The mechanism involved an initial oxidation to a relatively stable sulfoxide without ring-opening. Further oxidation of the sulfoxide involved two pathways: one which involved intermediate formation of an unstable sulfone and the other involves ring-opening coupled with oxidation through to the sulfonic acid. There was oligooscillatory production of aqueous bromine. Bromide produced in S1 reacts with excess bromate to produce aqueous bromine. The special stability associated with the sulfoxide allowed it to coexist with aqueous bromine since its further oxidation to the sulfone was not as facile. The direct reaction of aqueous bromine with NAHT was fast with an estimated lower limit bimolecular rate constant of 2.94 ± 0.03 × 10(2) M(-1) s(-1).

Mg ion implantation on SLA-treated titanium surface and its effects on the behavior of mesenchymal stem cell.

Magnesium (Mg) is one of the most important ions associated with bone osseointegration. The aim of this study was to evaluate the cellular effects of Mg implantation in titanium (Ti) surfaces treated with sand blast using large grit and acid etching (SLA). Mg ions were implanted into the surface via vacuum arc source ion implantation. The surface morphology, chemical properties, and the amount of Mg ion release were evaluated by scanning electron microscopy (SEM), Auger electron spectroscopy (AES), Rutherford backscattering spectroscopy (RBS), and inductively coupled plasma-optical emission spectrometer (ICP-OES). Human mesenchymal stem cells (hMSCs) were used to evaluate cellular parameters such as proliferation, cytotoxicity, and adhesion morphology by MTS assay, live/dead assay, and SEM. Furthermore, osteoblast differentiation was determined on the basis of alkaline phosphatase (ALP) activity and the degree of calcium accumulation. In the Mg ion-implanted disk, 2.3×10(16) ions/cm(2) was retained. However, after Mg ion implantation, the surface morphology did not change. Implanted Mg ions were rapidly released during the first 7 days in vitro. The MTS assay, live/dead assay, and SEM demonstrated increased cell attachment and growth on the Mg ion-implanted surface. In particular, Mg ion implantation increased the initial cell adhesion, and in an osteoblast differentiation assay, ALP activity and calcium accumulation. These findings suggest that Mg ion implantation using the plasma source ion implantation (PSII) technique may be useful for SLA-treated Ti dental implants to improve their osseointegration capacity.

Mandibular reconstruction with autologous human bone marrow stem cells and autogenous bone graft in a patient with plexiform ameloblastoma.

Ameloblastoma is a histologically benign tumor, but it shows a tendency of locally aggressive behavior. To our knowledge, this is the first report of a successful reconstruction performed for treating a mandibular defect by using autologous human bone marrow mesenchymal stem cells in a patient with plexiform ameloblastoma. In this article, we report the result of the mandibular reconstruction with autologous human bone marrow mesenchymal stem cells and autogenous bone graft, followed by the placement of osteointegrated dental implant and prosthodontic treatment in a patient with plexiform ameloblastoma.

Phlorotannin-rich Ecklonia cava reduces the production of beta-amyloid by modulating alpha- and gamma-secretase expression and activity.

Beta-amyloid (Aß) is a major pathogenic peptide in Alzheimer's disease (AD) and is generated by the processing of amyloid precursor protein (APP). We have previously reported that the brown algae Ecklonia cava, which has anti-oxidant and anti-inflammatory functions, decreased Aß production and further aggregation in HEK293 cells expressing the APP Swedish mutation. Here, we show the reduction mechanism of Aß production using the butanol extract of Ecklonia cava through the examination of expression and activity of alpha-, beta-, and gamma-secretase. Treatment with the extract resulted in the activation of alpha-secretase with a contrasting decrease in its mRNA and protein expression. This activation was consistent with the translocation of the extract into the plasma membrane of the secretase. Gamma-secretase activity was lowered by E. cava, and this effect may be due to the decreased expression of PSEN1 mRNA and protein. In addition, the basal nuclear location of PSEN1, which may affect chromosome missegregation in neurodegenerative disease, was reduced by the extract, despite the significance of this finding remains unclear. Taken together, these results led us to conclude that E. cava regulated the expression and activity of gamma-secretase and alpha-secretase, leading to a reduction in Aß production by the stable cells. Our data indicate that E. cava is a novel natural-product candidate for AD treatment, although further in vivo studies are needed.

Synchronous central giant cell granuloma and ossifying fibroma of the mandible.

Central giant cell granuloma (CGCG) is a benign lesion of the jaws. In most cases, the lesion presents as a painless, slow-growing swelling of the jaws. Ossifying fibroma (OF) of the jaw is a benign neoplasm that consists of variable amounts of mineralized material embedded in a fibrous stroma. The simultaneous occurrence of CGCG with odontogenic fibroma or OF has been described as combined lesions. However, synchronous presentation of CGCG and OF in the mandible is a rare occurrence. This report describes a case of 2 completely independent CGCG and OF located on both posterior regions of the mandible.